How neurons differentiate and make the appropriate synaptic connections is one of the major questions in modern biology. A powerful approach to determine the events of synapse formation is to use monoclonal antibodies (MAbs) and lectins as tools to analyze membrane molecules. We have recently demonstrated that a group of antigens from the eye of Drosophila are retained in the retina of mice, monkey and man. Moreover, some of these highly conserved antigens specifically identify photoreceptor (PR) or glial cells in fluorescence microscopy. Specific MAbs have been identified which stain different subcellular compartments of the PR cell. We have also found that peanut lectin (PNA), which recognizes galactose-galactosamine residues, can serve as a cell marker for cones. Our long term objectives are: (1) To test the hypothesis that PR differentiation results in the sequential development of surface glycoconjugates or antigens in the normal retina, and that alterations in these moieties play a role in abnormal PR development which results in degeneration. This hypothesis will be tested by comparing these marker molecules during differentiation in normal and PR degenerative mouse retinas. We will also examine the steps in the internal organization of the synaptic terminal of the PR cell by integrating the appearance of cytoskeletal elements with the known appearance of synaptic vesicles and ribbons. (2) To test the hypothesis that Mueller cells act as glial guides for the developing PR cells and/or the developing retinal vasculature. This hypothesis will be tested by using routine electron microscopy (EM) and immuno-EM methods to study the time window when PR cells are migrating and their relationship to glial cells. As illustrated in Drosophila, one may go from the pattern of differentiation of a specific cell type to the molecule(s) involved and ultimately to the gene. As our studies correlate the appearance of several highly conserved antigens with contemporaneous developmental events, our colleagues will be actively pursuing the purification and identification of the molecules bearing these epitopes.